In this NIH Recovery Act Funds for Competitive Revision Application proposal, we propose to leverage the unique rich data set available from the NIDDK-funded Chronic Renal Insufficiency Cohort (CRIC) study, as related to its principal aims of better understanding factors associated with progression of chronic kidney disease (CKD). The goal is to significantly expand the scope of the original study by adding comprehensive genotyping as an added dimension of critical variables to be studied in the context of progressive CKD and related outcomes. Our primary hypothesis is that unidentified gene variants contribute significantly to the variable progressive loss of renal function in subjects with established CKD. The CRIC study is a large prospective, multi-center, CKD cohort with 3939 participants. We plan to complete a genome-wide genotyping on 3750 participants who have consented for genetic studies using the Affymetrix(R) 6.0 array. We will be able to take advantage of the serial standardized measurement of numerous CKD risk factors and intermediate phenotypes and plan to associated SNP markers and copy number variants with renal outcomes including change in glomerular filtration rate, time to development of end-stage renal disease, and change in measures of cystatin C. We will also investigate potential pathways and effect modifiers of our top identified gene variants. All statistical analyses will be undertaken separately within white (CEU) and African American (AA) participants. We will replicate our findings in silico using existing genome-wide results available from several large cohort studies representing Caucasian and AA subjects without CKD. RELEVANCE: The results from this study is expected to increase our understanding the genetic underpinning of progressive CKD and associated outcomes.